Impaired and delayed wound healing are significant problems in diabetics. Furthermore, aging and diabetes together further compound the problem. These observations have created interest in pharmacologic enhancement of healing with growth factors involved in the body?s wound repair process. Clinical trials have been discouraging, with only modest improvement in wound repair in humans. Studies indicate that cells in healing-impaired individuals may fail to respond adequately to growth factors. Thus, wound healing in such individuals may not be improved by growth factor treatment, but may require administration of downstream factors normally induced in cells in response to growth factors involved in healing, but not induced in cells of those with poor wound healing capability. In Phase I of this proposal, a particular factor that is strongly implicated as a critical component of wound healing in the body, and whose expression is normally induced by growth factors, will be tested for its ability to enhance wound healing in diabetic mice. If successful, this factor will be developed in Phase II as a clinical wound-healing agent, particularly for those with impaired wound healing, such as diabetics. PROPOSED COMMERCIAL APPLICATION: Wound treatment costs total billions of dollars (almost $10 billion for pressure ulcers alone). Impaired and delayed wound healing affect more than a half million individuals annually and are significant problems in diabetics (over 15 million diabetics are in the U.S.) and the elderly. Impaired/delayed healing also has severe impact on ischemia that leads to heart attacks (the leading cause of mortality) and limb amputations.